AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 6 1431-R1436, Copyright © 1994 by American Physiological Society
Tumor necrosis factor-alpha and fever after peripheral inflammation in the rat
A. L. Cooper, S. Brouwer, A. V. Turnbull, G. N. Luheshi, S. J. Hopkins, S. L. Kunkel and N. J. Rothwell
University of Manchester, United Kingdom.
The involvement of endogenous tumor necrosis factor-alpha (TNF-alpha) in
the pyrogenic [i.e., rise in colonic temperature (Tc)] and thermogenic
[increase in oxygen consumption (VO2)] responses to inflammation was
investigated in rats subjected to an intramuscular injection of turpentine.
Turpentine administration caused a rise in Tc and VO2 within 2 h (0.9 +/-
0.1 degrees C, 27 +/- 2%, respectively). Eighteen to twenty hours after
turpentine, the magnitude of these responses had increased (2.3 degrees C
fever and a 28% increase in metabolic rate compared with control animals)
and was associated with marked inflammation in the injected limb. A rapid
(by 4 h) and sustained rise in the plasma concentration of the endogenous
pyrogen IL-6, but not TNF-alpha, was also observed. Intravenous
pretreatment with a TNF-alpha antiserum attenuated the rise in Tc observed
2, 8, and 18 h after turpentine injection and almost abolished the
hypermetabolic response observed at 18 h. In addition, the TNF-alpha
antiserum inhibited the peak rise (8 h) in plasma IL-6 by 76%. These
findings indicate that endogenous TNF-alpha is involved in fever and
hypermetabolism during inflammation and that it may exert these effects by
inducing the release of IL-6 into circulation.
